New Zealand Patent Nos. 191413 and 193807 of ICI Tasman Limited disclose water based formulations of D, L-tetramisole and clostridial vaccine in the treatment of helminthiasis and clostridial diseases in warm-blooded animals. Both D, L-tetramisole and the clostridial vaccine are water soluble hence a combination of the two is straight forward. What was surprising was that the clostridial vaccine remained effective at a pH lower than 6.0 and that the combination improved the immune response in ruminants, though not in other animals.
These aqueous formulations commonly used an adjuvant such as alum or alum hydroxide to enhance the effect of the antigen. Such adjuvants are usually included in the formulation as an aqueous suspensions. The vaccines can then be readily mixed with water based anthelmintic formulations.
Since the use of D, L-tetramisole and more particularly the L-isomer levamisole, there have been a number of other potent antiparasitic macrocyclic lactone compounds such as the avermectins, ivermectin, doramectin, abamectin, milbemycin, moxidectin used in the treatment of diseases in warm blooded animals. These later parasiticides are insoluble in water which creates difficulties in formulating stable injectable compositions. However, the compounds have the advantage that they are active against internal and external parasites in domestic animals.
Formulations are therefore based on co-solvent systems or aqueous solvent Systems utilising a water-soluble solvent with one or more wetting agents. Water soluble solvents mix readily with traditional aqueous adjuvant systems to form combinations of anthelmintics and vaccines. This is not the case with oil based (non-aqueous) systems.